tbuckley/cabot-search huggingface dataset:
PB2528: THE IMPACT OF ZINC SUPPLEMENTATION ON HYPERBILIRUBINEMIA IN SICKLE CELL DISEASE
Authors: Mohammed Al Farttoosi
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle cell hepatopathy is a common complication of sickle cell disease (SCD). The symptoms of sickle cell hepatopathy can range from mild to severe, and the condition can progress to cirrhosis and liver failure. Jaundice is a common complaint in individuals with SCD. Zinc may be deficient in sickle cell disease patients caused by a decrease in its bioavailability due to hemolysis, or due to decreased dietary intake of zinc. Aims: To assess the impact of zinc supplementation on hyperbilirubinemia in SCD Methods: a cohort of patients (n=47), registered and followed-up at Basra’s adult hereditary blood diseases center, with clinical jaundice and a total serum bilirubin of 3 mg/dl or more, no history of hepatitis or any liver disease or injury, patients were given zinc supplements daily for a month, a pre-zinc and a post-zinc TSB level was recorded. Results: there was a highly significant decrease (p=0.00016) in TSB, of 1.7 mg/dl in average, the decrease was higher in sickle cell anemia (SS) than in sickle thalassemia, (p=0.03), there was no effect of hemoglobin level and cholecystectomy status on the decrease level. Summary/Conclusion: zinc at supplementation dose can reduce jaundice in SCD, a larger sample and a longer follow up is required Keywords: Hyperbilirubinemia, Sickle cell disease, Zinc
PB2589: EFFICACY AND SAFETY OF ABCD IN THE TREATMENT OF INVASIVE ASPERGILLOSIS IN PATIENTS WITH HEMATOLOGIC DISEASES
Authors: Aiming Pang, Jinhai Ren, Guangxun Gao, Yicheng Zhang, Sizhou Feng
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Amphotericin B colloidal dispersion (ABCD) has less renal toxicity than traditional amphotericin B. There is no evidence of ABCD made in China in patients with hematologic diseases complicated with IFD. Aims: The purpose of this study was to evaluate the efficacy and safety of ABCD made in China in the treatment of invasive aspergillosis in patients with hematologic diseases. Methods: In this multi-center, one-arm study, 65 patients with invasive aspergillosis were enrolled to receive ABCD antifungal therapy with a treatment of 28 days. The primary endpoint was the treatment response rate, and the secondary endpoint was the incidence of ABCD related adverse events. Results: By September 2022, a total of 22 patients were enrolled for interim analysis. Safety was assessed in all enrolled patients, and efficacy was assessed in 16 patients (72.7%) who were treated for at least 1 week. The median age was 42.5 years (range 18-68), and the underlying disease was mainly acute myeloid leukemia (n= 19,86.4%). Most of the enrolled patients showed characteristic pulmonary aspergillus infection (n=21, 95.5%), and Aspergillus was detected by microbiology in 2 cases (9.1%). In this study, 81.8% (n=18) patients had a history of antifungal therapy, and were switched to ABCD after treatment failure (n= 6, 27.3%) or prevention breakthrough (n=12, 54.5%). The median treatment time of ABCD was 16 (range 1-28) days, and the average daily dose of ABCD was (2.3±0.7) mg·kg-1·d-1. The effective rate was 81.3% (13/16). 9.1% (n=2) of patients stopped treatment early due to infusion reaction, suggesting that attention should be paid to the prevention and treatment of infusion reaction in clinical treatment. Grade 3/4 adverse events included fever (4.5%), hypokalemia (31.8%), and increased alanine aminotransferase (9.1%), without grade 3/4 increased creatinine, indicating low renal toxicity of ABCD. Summary/Conclusion: ABCD made in China has shown good clinical efficacy and acceptable toxicity in the treatment of invasive aspergillus disease, especially low renal toxicity, which provides a new choice for antifungal therapy. Keywords: Hematological malignancy, Invasive aspergillosis, Clinical outcome, Amphotericin
P1646: A SYSTEMATIC REVIEW AND META‐ANALYSIS OF RANDOMIZED CONTROLLED TRIALS ON PRIMARY AMBULATORY THROMBOPROPHYLAXIS (PATP) IN PATIENTS WITH LYMPHOMA RECEIVING CHEMOTHERAPY
Authors: Thura Htut, Kyaw Thein, Yin Myat, Myat Han, Thein Oo
Journal: HemaSphere (2023)

Topic: 34. Thrombosis and vascular biology - Biology & Translational Research Background: Venous thromboembolism (VTE) is a frequent complication of cancer and cancer treatment. Lymphoma is a highly thrombogenic cancer according to the Khorana score (KS) in outpatient setting. Lymphoma cells promote thrombin generation by several mechanisms and can also cause lymphadenopathy-related venous stasis. Systemic anticancer therapy can disrupt endothelium and enhance the procoagulant effect of neoplastic cells by several mechanisms, and therefore, yields an additional risk factor for VTE. Cancer‐associated thrombosis is the second leading cause of death in cancer patients. Recently, PATP in solid cancer patients were performed in trials to decrease VTE rates with the aim to improve survival. Aims: We performed a systematic review and meta‐analysis of randomized controlled trials (RCTs) to determine the benefit of PATP in lymphoma patients who were on chemotherapy. Methods: We conducted a literature search using MEDLINE and EMBASE databases through January 31, 2023 using the following keywords; ‘low‐molecular weight heparin’ OR ‘direct oral anticoagulant’ AND ‘lymphoma. The RCTs with reduction in VTE as a primary or secondary end‐point were incorporated in the analysis. The primary meta‐analytic approach was a random effects model using the Mantel–Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with I2 and Cochran’s Q‐ statistic. A ‘P value’ of <0·05 was considered significant and I2 > 50% was considered substantially heterogeneous. Results: 202 patients from subsets of two RCTs (AVERT and CASSINI) were included in our meta‐analysis. Both AVERT and CASSINI trials enrolled patients with lymphoma, KS ≥ 2. Apixaban 2.5 mg twice daily and rivaroxaban 10 mg once daily were prescribed for 6 months in AVERT and CASSINI trials, respectively. The randomization ratio was 1 to 1 in both studies. The I2 statistic showed moderate heterogeneity among RCTs. The VTE incidence was similar (4·9%) in both groups. The pooled RR was not significant at 1.02 (95% CI: 0·24–4.42, P = 0·28). The absolute RD was −0·01 (95% CI: −0·09 to 0·07, P = 0·19). Summary/Conclusion: Our analysis showed that there was no reduction in VTE rates by providing PATP to ambulatory lymphoma patients who were on chemotherapy. Hence, routine PATP should not be recommended in ambulatory patients with lymphoma. Further RCTs are needed to determine the high‐risk subset of lymphoma patients who may benefit from PATP.Keywords: Thromboprophylaxis, Lymphoma, Chemotherapy, Thrombosis
REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial
Authors: Javier Martin-Broto, Claudia Valverde, Nadia Hindi, Bruno Vincenzi, Javier Martinez-Trufero, Giovanni Grignani, Antoine Italiano, Javier Lavernia, Ana Vallejo, Paolo Dei Tos, Francois Le Loarer, Ricardo Gonzalez-Campora, Rafael Ramos, Diana Hernández-Jover, Antonio Gutierrez, Cesar Serrano, Maria Monteagudo, Rocio Letón, Mercedes Robledo, David S Moura, Marta Martin-Ruiz, Jose A López-Guerrero, Julia Cruz, Antonio Fernandez-Serra, Jean-Yves Blay, Elena Fumagalli, Virginia Martinez-Marin
Journal: Molecular Cancer (2023)

Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST.Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment.From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST.Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST.ClinicalTrials.gov Identifier: NCT02638766.
P1554: SYSTEMATIC REVIEW OF EXTENDED VERSUS BOLUS INFUSION OF BROAD-SPECTRUM BETA-LACTAM ANTIBIOTICS FOR FEBRILE NEUTROPENIA
Authors: Kazuhiro Ishikawa, Koko Shibutani, Fujimi Kawai, Erika Ota, Osamu Takahashi, Nobuyoshi Mori
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Extended infusion (EI) of beta-lactam antibiotics may be more clinically effective than bolus infusion (BI) in patients with severe sepsis, with several studies reporting good outcomes in patients with febrile neutropenia (FN). Aims: We conducted this systematic review to compare EI and BI of beta-lactam antibiotics in patients with FN Methods: Two reviewers independently searched for articles from PubMed, Embase, and Ichushi. Selection criteria included clinical trials comparing EI with BI of beta-lactam antibiotics as an empirical treatment for FN in patients with hematologic malignancies and evaluating clinical response, all-cause mortality, and adverse events. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated. Results: Three articles (2 randomized controlled trials; RCTs and one retrospective study) were included from 2011 to 2018. Clinical response was assessed with an RR [95% CI] of 1.17[0.94,1.45] and heterogeneity (χ2=2.32; p=0.13; I2=57%) in 2 RCTs and with an RR [95% CI] of 1.67[1.25,2.24] in one retrospective study. All-cause mortality was assessed with an RR [95% CI] of 1.36[0.44,4.25] and heterogeneity (χ2=0.62; p=0.43; I2=0%) in 2 RCTs, and with an RR [95% CI] of 0.39[0.13,1.15] in one retrospective study. Only one RCT evaluated adverse events, with an RR [95% CI] of 0.46 [0.13,1.65]. Summary/Conclusion: EI of beta-lactam antibiotics did not show better in mortality compared to BI. However, it may be better because of its favorable outcomes and fewer adverse events, even if not significant. Since evidence is limited owing to the small number of studies, further randomized controlled studies are desirable.Keywords: Infection, Neutropenia, Fever, Febrile neutropenia
P1336: LONGTERM EX VIVO EXPANSION OF FUNCTIONAL MURINE AND HUMAN HEMATOPOIETIC STEM CELLS USING BONE-LINING STROMAL CELLS
Authors: Lukas Klein, Shubhankar Sood, Franziska Pilz, Pit Albert, Ramon Barrull Mascaró, Sonia Fernandez Torices, Nanni Schmitt, Daniel Nowak, Marieke Essers
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Hematopoietic stem cells (HSCs) have the potential to treat various hematological disorders, but the limited availability of HSCs for transplantation remains a significant clinical challenge. Ex vivo expansion of HSCs is a promising approach to overcome this shortcoming, but current methods have limitations, such as reduced self-renewal capacity and differentiation potential. While there have been recent attempts to expand HSCs using optimized media, stable ex vivo expansion of HSCs remains limited. Given the substantial clinical importance of HSCs for bone marrow transplantation, robustly functioning systems with preservation of HSC self-renewal ex vivo are urgently needed. Aims: The aim of this study is to investigate the potential of functionally defined bone lining reinvigorated mesenchymal stem cells (rMSCs) to facilitate ex vivo expansion of both murine and human hematopoietic stem cells (HSCs) with importance to clinical hematology. Methods: Using bone digestion followed by flow cytometry, bone-lining mesenchymal stromal cells were successfully isolated, cultured and expanded, and subsequently long-term co-cultured with HSCs. The isolation process established in mice was successfully implemented in the human system using human femur bones for the isolation of the stromal cells. Results: We have established a reproducible and robust protocol for the isolation and subsequent expansion of bone-lining rMSCs, functionally defined by their capability to ex vivo maintain and expand HSCs. During long-term in vitro expansion together with rMSCs, HSCs retained their phenotypic stem cell state with functional bone marrow reconstitution capacity. Additionally, the co-culture system allowed for clonal expansion of single HSCs, which could have exciting applications in rare diseases and may significantly reduce the number of experimental animals required for HSC analysis. The isolation process for rMSCs established in mice was successfully implemented in the human system, and initial co-culture experiments of human rMSCs and human HSCs suggest similar maintenance and expansion of human HSCs ex vivo. Summary/Conclusion We could show that growth-promoting, functionally defined rMSCs can be used in a co-culture with HSCs to effectively ex vivo maintain and expand functional HSCs. The results suggest exciting new research and therapeutic opportunities for gene therapy and personalized medicine Keywords: Bone Marrow, Hematopoietic stem cell, Mesenchymal stem cell, Ex vivo expansion
P1484: THE DANISH SCREENING PROGRAM FOR HEMOGLOBINOPATHIES: A 16-YEAR REVIEW
Authors: Esther Gravholt, Jesper Petersen, Mathis Mottelson, Amina Nardo‐marino, Mathias Rathe, Marianne Olsen, Charlotte Holm, Finn Jørgensen, Henrik Birgens, Andreas Glenthøj
Journal: HemaSphere (2023)

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Screening programs for hemoglobinopathies have been present for decades in endemic areas but is lacking in many low-prevalence countries. Despite increasing prevalence of hemoglobinopathies in the Nordic countries, screening programs have yet to be implemented in most. The Danish screening program for hemoglobinopathies seek to detect parental carrier state of hemoglobinopathy antenatally by offering hemoglobinopathy testing through general practitioners to at-risk women of reproductive potential before 13th week of gestation. Aims: To evaluate the Danish hemoglobinopathy screening program over a period of 16 years, from January 2007 to December 2022, as a program suited for a low-prevalence country with an at-risk minority. Methods: Retrospective register-based study, using the laboratory database of the Danish Red Blood Cell Center as our source register, covering 77% of the Danish population. Results: During the study period, we observed more than a fivefold increase in the number of diagnostic examinations for hemoglobinopathies performed yearly, from 640 examinations in 2007 to 3,932 examinations in 2022, the majority in women of the reproductive age. We diagnosed 5,142 individuals with thalassemia trait and 871 individuals with sickle cell trait. 136 individuals were diagnosed with thalassemia intermedia/major, sickle cell disease, or Hb Bart’s. 61/136 were children born during the study period. 23/61 were born from mothers not living in Denmark during the 1st trimester of pregnancy and thus not available for the Danish screening program. Prenatal invasive testing for hemoglobinopathies was performed on 60 fetuses with 12 being homozygous/compound heterozygous for a serious hemoglobinopathy. Summary/Conclusion: The Danish screening program for hemoglobinopathies has provided diagnostics and a reproductive choice to a substantial number of women. Adherence to the screening program is a subject of further investigation and optimization. Acknowledgement: This project is carried out within the framework of European Reference Network on Rare Hematological Diseases (ERN-EuroBloodNet)—Project ID No 10108571. ERN-EuroBloodNet is partly co-funded by the European Union within the framework of the Fourth EU Health Program.Keywords: Screening, Sickle cell disease, Hemoglobinopathy, Thalassemia
PB2407: ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (ALLO-HSCT) WITH CYCLOPHOSPHAMIDE IN PEDIATRIC HIGH-RISK ACUTE MYELOID LEUKEMIA (HR-AML)
Authors: Ming Sun, Hao Xiong, Zhi Chen
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for pediatric high-risk acute myeloid leukemia (HR-AML). The timing of HSCT for HR-AML remains controversial. Few studies have reported the outcomes in pediatric AML patients treated with allo-HSCT with post-transplant cyclophosphamide (PTCy) regimen. Aims: The present retrospective study was to evaluate the outcomes of pediatric HR-AML patients who underwent allo-HSCT with PTCy regimen following 2–3 blocks of chemotherapy irrespective of the minimal/measurable residual disease (MRD) status. Methods: Forty-six newly diagnosed HR-AML patients aged < 18 years old who underwent HSCT with PTCy following 2-3 blocks of chemotherapy between July 1, 2018 and March 1, 2022, at Wuhan Children’s Hospital were enrolled. The follow-up endpoint was the time of death or July 31, 2022. The Shapiro-Wilk normality test was used to check for data normality. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method. All p-values were two-sided and p < 0.05 was considered statistically significant. Results: The median follow-up time was 24.9 (range: 3.9–48.7) months. The median age at transplantation was 5.23 (range: 0.9–16.2) years. Three patients received HLA matched sibling donors’ transplants, while 43 received haploidentical donors (HID) transplants. All patients received peripheral blood stem cells (PBSCs) and achieved successful donor cell engraftment. The median mononuclear cell (MNC) and CD34+ cell counts were 21.5 ×108/kg (range: 6.56–35.7 ×108/kg) and 13.5 ×106/kg (range: 4.05–25.55 ×106/kg) at transplantation, respectively. The engraftment rate was 100% with median times to engraftment for neutrophils > 500/µL and platelets > 20,000/µL of 15 (range: 13–20) days and 15.5 (range: 10–40) days, respectively. Grade III–VI acute GVHD occurred in 8 (17.4%), while chronic GVHD occurred in 6 (13.%) patients; one patient died due to chronic GVHD. The estimated 4-year OS and RFS were 86.2% and 86.3%, respectively. The cumulative incidence of relapse at 4 years was 13.7% (95% CI: 2.8–23.3%). Pre-transplantation MRD positive rate was 43.5% (20/46). Surprisingly, MRD positive group showed higher OS (94.7% [95% CI: 85.2–100.0%] vs. 79.3% [95% CI: 64.6–97.4%]) and RFS (94.7% [95 CI: 85.2–100.0%) vs. 79.3% [95% CI: 64.6–97.4%]) than the MRD negative group. Summary/Conclusion: Our study demonstrated the safety and efficacy of allo-HSCT with PTCy for in HR-AML pediatric patients. Allo-HSCT with PTCy regimen should be considered as a potential treatment for HR-AML pediatric patients who received 2–3 blocks of routine chemotherapy regardless of the pre-Tx MRD status. Further studies are required to confirm findings Keywords: AML, Cyclophosphamide, Allogeneic stem cell transplant, Survival
Determinants of Influenza A infection rate in post-COVID-19 era
Authors: Isabell Wagenhäuser, Juliane Mees, Julia Reusch, Thiên-Trí Lâm, Alexandra Schubert-Unkmeir, Lukas B. Krone, Anna Frey, Oliver Kurzai, Stefan Frantz, Lars Dölken, Johannes Liese, Alexander Gabel, Nils Petri, Manuel Krone
Journal: Journal of Infection (2023)
PB2526: UMBILICAL CORD BLOOD SCREENING FOR SICKLE CELL DISEASE: A PILOT STUDY IN THE NORTH OF TUNISIA
Authors: Houyem Ouragini, Sana Zitouni, Dorra Chaouachi, Amira Ayachi, Machaal Mourali, Samia Menif
Journal: HemaSphere (2023)

Topic: 26. Sickle cell disease Background: Sickle cell disease (SCD) is one of the most common monogenic diseases with multiple phenotypic expressions that can cause lifelong disabilities and/or early mortality. Early diagnosis of SCD through neonatal screening is a cost-effective intervention, which reduces adverse outcomes related to SCD and mortality. Aims: For the first time in Tunisia and in North of Africa, we initiated a pilot study on newborn screening for SCD based on umbilical cord blood (UCB). Methods: UCB was collected at Bizerte’s “Habib Bougatfa” hospital, North Tunisia, between April and May 2018, and January and May 2019 (22 weeks). The inclusion criteria for the newborns were: gestational age greater than 36 weeks, no complications during pregnancy or delivery for mother or neonate, no intrauterine transfusions, and vaginal delivery. Umbilical cord blood samples were analysed by capillary electrophoresis (CE) to reveal phenotypes for HbSS and HbAS and genotype was confirmed by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Complete blood count was also carried out for all the samples. This study was approved by the Pasteur Institute’s Biomedical Ethics Committee, Tunisia Results: During the study period, a total of 404 samples were collected. There was no maternal contamination in any sample. Seven out of them were diagnosed as HbAS. The result was confirmed by PCR RFLP for all of them. For these infants, the mean level of red blood cells was 4.44.106/mm, Hb=15.61g/dL, MCV=108.03µm3 and MCHC=32.47g/dL. The estimated mean percentages of HbA, HbF and HbS were 10,9%, 82,5%, and 6,6%, respectively. No SCD was detected. Summary/Conclusion: There were 7 infants with sickle cell trait, resulting in a carrier frequency of 1.7% in Northern Tunisia. Neonatal screening involving the use of cord blood samples is easier, less invasive, and more accepted by parents. Moreover, the important volume of samples allows several tests to be applied. Identification of affected infants should permit anticipation and, hopefully, prevention of major catastrophic complications that contribute to the high mortality for SCD in the first years of life. Thus, neonatal testing involving the use of UCB samples and CE has shown its effectiveness and can be used for implementation of newborn screening for SCD in Tunisia. Keywords: Cord blood, Sickle cell disease, Screening
On the relevance of thrombomodulin variants in atypical hemolytic uremic syndrome
Authors: Ana Huerta, Emi Arjona, Jose Portoles, Paula Lopez-Sanchez, Teresa Cavero, Jeanette Fernandez-Cusicanqui, Miquel Blasco, Virginia Cabello, Natividad Calvo, Montserrat Diaz, Maria Herrero-Goñi, Mireia Aguirre, Sandra Elías, Maria Paz Alcaide, Natalia Ramos, Joana Sellares, Santiago Rodríguez de Córdoba
Journal: Kidney International (2023)

Atypical Hemolytic Uremic Syndrome (aHUS) is a potentially-lethal medical condition often resulting in chronic kidney disease (CKD). 1 Genetic testing is critical in clinical care since pathogenic variants in complement genes account for 50-60% of cases of aHUS 1,2 and their identification reinforce diagnosis and assist clinical decisions such as treatment with anti-complement drugs.1,3 One gene of interest is THBD, which encodes thrombomodulin (TM), an anti-coagulant endothelial membrane glycoprotein that also regulates complement by binding to factor H and accelerating the inactivation of C3b.